Higher maintenance cyclosporine dose decreases the risk of graft failure in North American children: a report of the North American Pediatric Renal Transplant Cooperative Study.
Because of changing cyclosporine dosing patterns over the years, maintenance doses in 1469 living donor and 1486 cadaver donor index renal transplants in patients who were 0 to 20 yr of age of the time of transplantation were reviewed. All grafts had at least 30 days' function. Eighty-nine percent of living donor patients and 95% of cadaver donor patients were maintained on cyclosporine for 12 months after transplantation. Among patients receiving cyclosporine, the maintenance 12-month dose in living donor graft recipients increased from 6.4 mg/kg per day for patients who had transplants done in 1987 to 7.9 mg/kg per day for patients who had transplants done in 1992 (P = 0.02). Among cadaver donor graft recipients, the mean 12-month maintenance dose increased from 6.4 mg/kg per day in 1987 to 7.8 mg/kg per day in 1992 (P = 0.01). At 6 months after transplantation, the maintenance cyclosporine dose in 1103 living donor graft recipients who retained graft function during the subsequent 6-month period was 7.1 mg/kg per day, compared with a 6-month dose of 3.9 mg/kg per day in 28 patients who lost their graft in the subsequent 6-month period. For 1041 recipients of cadaver donor grafts who retained graft function through 12 months after transplantation, the 6-month maintenance cyclosporine dose was 7.4 mg/kg per day, compared with 5.4 mg/kg per day in 59 patients whose graft failed in the subsequent 6 months. In patients who did not have an acute rejection episode during the first 12 months after transplantation, the rate of subsequent "late" rejections was 22% for patients with a 12-month maintenance cyclosporine dose < or = 4.0 mg/kg per day, and 16% for patients whose 12-month maintenance cyclosporine dose exceeded 8.6 mg/kg per day. A proportional hazards regression analysis, using cyclosporine dose as a time-dependent covariate, showed that the hazard of graft failure was reduced 5 to 6% for each incremental increase of 1 mg/kg maintenance dose of cyclosporine (within the dose range studied) for both living and cadaver donor source transplants.